Research Summary: Sustained Reperfusion after Blockade of Glycoprotein-Receptor-Ib in Focal Cerebral Ischemia: An MRI Study at 17.6 Tesla

ABSTRACT

Background

Inhibition of early platelet adhesion by blockade of glycoprotein-IB (GPIb)
protects mice from ischemic stroke. To elucidate underlying mechanisms
in-vivo, infarct development was followed by ultra-high field MRI at 17.6
Tesla.


Methods

Cerebral infarction was induced by transient-middle-cerebral-artery-occlusion
(tMCAO) for 1 hour in C57/BL6
control mice (N = 10) and mice treated with 100
µg Fab-fragments of the GPIb blocking antibody p0p/B 1 h after
tMCAO
(N = 10). To control for the effect of reperfusion,
additional mice underwent permanent occlusion and received
anti-GPIb treatment (N = 6;
pMCAO) or remained without
treatment (N = 3;
pMCAO). MRI 2 h and 24 h after MCAO
measured cerebral-blood-flow (CBF) by continuous arterial-spin labelling,
the apparent-diffusion-coefficient (ADC), quantitative-T2 and T2-weighted
imaging. All images were registered to a standard mouse brain MRI atlas and
statistically analysed voxel-wise, and by cortico-subcortical ROI
analysis.


Results

Anti-GPIb treatment led to a relative increase of
postischemic CBF vs. controls in the cortical territory of the MCA (2 h:
44.2±6.9 ml/100 g/min versus 24 h: 60.5±8.4;
p = 0.0012,
F(1,18) = 14.63) after
tMCAO. Subcortical CBF 2 h after
tMCAO was higher in
anti-GPIb treated animals (45.3±5.9 vs.
controls: 33.6±4.3; p = 0.04). In both regions,
CBF findings were clearly related to a lower probability of infarction
(Cortex/Subcortex of treated group: 35%/65% vs. controls:
95%/100%) and improved quantitative-T2 and ADC. After
pMCAO,
anti-GPIb treated mice developed similar infarcts
preceded by severe irreversible hypoperfusion as controls after
tMCAO indicating dependency of
stroke protection on reperfusion.


Conclusion

Blockade of platelet adhesion by anti-GPIb-Fab-fragments
results in substantially improved CBF early during reperfusion. This finding
was in exact spatial correspondence with the prevention of cerebral
infarction and indicates in-vivo an increased patency of the
microcirculation. Thus, progression of infarction during early ischemia and
reperfusion can be mitigated by anti-platelet treatment.

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Publisher: Public Library of Science

Date Published: 1-April-2011

Author(s): Pham M., Helluy X., Kleinschnitz C., Kraft P., Bartsch A., Jakob P., Nieswandt B., Bendszus M., Stoll G.

Link: https://doi.org/10.1371/journal.pone.0018386

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